IL6ST p.Ser780=
c.2340C>T · rs142623813 · VCV1164182
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.325%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.5 |
| Overall | ||
| CADD | 0.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.325%
African / African-American · 244/75,000 alleles
Filtering AF
0.292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.279%
Overall
0.0182%
294/1,614,058 alleles · rare
exomes 150/1,461,846 · genomes 144/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.325% | 307 |
| Admixed American | 0.0383% | 2,609 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,465 |
| East Asian | 0.00668% | 14,962 |
| South Asian | 0.00439% | 22,766 |
| European (non-Finnish) | 0.000508% | 196,665 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- IL6ST
- Protein
- p.Ser780=
- Coding
- c.2340C>T
- MANE Select
- NM_002184
- dbSNP
- rs142623813
- Type
- single nucleotide variant
- Location
- chr5:55941499 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.94 · 20 PDB
- Residue 780
- a UniProt-annotated variant site (in stws2; results in impaired cytokine-mediated signaling pathway with loss of response to il-6, il-11, il-27, osm and lif; does not localize to the cell membrane); a UniProt-annotated variant site (in hies4a; results in impaired cytokine-mediated signaling pathway with loss of response to il-6, il-11, osm and lif and a weak response to il-27); a UniProt-annotated variant site (in hies4a; results in impaired cytokine-mediated signaling pathway with loss of response to il-6, il-11, osm, lif and a weak response to il-27)
Similar variants
- IL6ST p.Arg281Ter Pathogenic ★★ same type
- IL6ST c.1552+3A>C Uncertain significance ★★ same type
- IL6ST c.658+6T>G Uncertain significance ★★ same type
- IL6ST p.Ala11Gly Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala174Gly Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala278Gly Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala278Val Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala517Pro Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/il6st-p-ser780 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown